The Role of PRIP in Breast Cancer

Abstract : Estrogen plays an important role in the normal breast and breast cancer development. Estrogens exert their cellular effects through ER that is a member of nuclear receptor superfamily. PRIP (Peroxisome proliferator receptor interacting protein) is a nuclear receptor coactivator that is amplified and overexpressed in breast cancer. The proposal was to investigate how the PRIP dysregulation contributes to abnormal growth and neoplastic development of breast. During the 3-year period, we dismpted PRIP gene in mice by homologous recombination. Mice nullizygous for PRIP died between embryonic day 11.5 and 12.5 (post coitum), indicating that PRIP like PBP, CBP, and p300 is an essential and nonredundant coactivator. We generated a conditional null mutation of PHP in mammary gland. Null mutation of PRIP in mammary gland causes defective mammopoiesis, demonstrating that PRIP is important for the normal mammary gland development. We isolated PIMT and PRMT2 as two components in the estrogen receptor transcriptional activation, advancing our understanding of estrogen signaling pathway. We found that PRIP overexpression occurs in about 60% and gene amplification occurs 10% of the breast cancers, suggesting that this coactivator plays an important role in the breast cancer development.